Pharmaceutical combination for the treatment of cancer

Abstract

The present invention relates to a pharmaceutical combination comprising a CDK inhibitor and at least one antioxidant enzyme inhibitor for use in the treatment of cancer. The present invention also relates to a method for the treatment of cancer comprising administering to a subject in need thereof, a therapeutically effective amount of a CDK inhibitor and a therapeutically effective amount of at least one antioxidant enzyme inhibitor. The pharmaceutical combination of the present invention exhibits synergistic effect when used in the treatment of cancer.

We claim: 
     
       1. A pharmaceutical kit for use in a combination therapy with an antioxidant enzyme inhibitor in the treatment of head and neck cancer, lung cancer, gastrointestinal cancer, blood and/or lymphatic system cancer, or breast cancer, the kit comprising:
 1) the cyclin-dependent kinase (CDK) inhibitor voruciclib, 
 2) the antioxidant enzyme inhibitor, and 
 3) a package insert, 
 wherein the package insert comprises instructions for administering voruciclib in combination with the antioxidant enzyme inhibitor for the treatment of head and neck cancer, lung cancer, gastrointestinal cancer, blood and/or lymphatic system cancer, or breast cancer in a subject in need thereof. 
 
     
     
       2. The pharmaceutical kit of  claim 1 , wherein the antioxidant enzyme inhibitor is selected from a glutathione peroxidase inhibitor, a glutathione reductase inhibitor, a glutathione transferase inhibitor, a gamma-glutamate cysteine ligase inhibitor, a glutathione synthetase inhibitor, a thioredoxin reductase (TrxR) inhibitor, an NADPH oxidase inhibitor, a catalase inhibitor, a peroxiredoxin inhibitor, and a superoxide dismutase inhibitor. 
     
     
       3. The pharmaceutical kit of  claim 1 , wherein the antioxidant enzyme inhibitor is a thioredoxin reductase (TrxR) inhibitor. 
     
     
       4. The pharmaceutical kit of  claim 3 , wherein the TrxR inhibitor is selected from auranofin, ebselen, and arsenic trioxide. 
     
     
       5. The pharmaceutical kit of  claim 1 , further comprising an additional CDK inhibitor. 
     
     
       6. The pharmaceutical kit of  claim 5 , wherein the additional CDK inhibitor is selected from palbociclib, dinaciclib, seliciclib, milciclib, LEE-011, bemaciclib, 7-hydroxy staurosporine, alvocidib, JNJ-7706621, BMS-387032, AT7519M, riviciclib, roniciclib, ZK-304709, ON-123300, CYC-065, LS-007, PHA-793887, TG-02, olomoucine, and purvalanol A. 
     
     
       7. The pharmaceutical kit of  claim 1 , wherein the package insert further comprises information about the indication, usage, doses, direction for administration, contraindications, precautions, and warnings. 
     
     
       8. The pharmaceutical kit of  claim 1 , further comprising a pharmaceutically acceptable buffer, water for injection, phosphate-buffered saline, Ringer's solution, or dextrose solution. 
     
     
       9. The pharmaceutical kit of  claim 1 , wherein voruciclib comprises (+)-2-(2-chloro-4-trifluoromethylphenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methylpyrrolidin-3-yl)-chromen-4-one, or a salt thereof. 
     
     
       10. The pharmaceutical kit of  claim 1 , wherein voruciclib comprises (+)-2-(2-chloro-4-trifluoromethylphenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methylpyrrolidin-3-yl)-chromen-4-one hydrochloride.